Appropriate dosing of parenteral medications such as antibody preparations is a critical factor in their administration to patients. One aspect of the requirement for safe and effective dosing schemes is that infusion reactions are occasionally associated with administration of antibody preparations to patients. In the field of anticancer therapy, infusion reactions have been reported in association with the administration of several antibody-targeted therapeutics, including rituximab, trastuzumab, bevacizumab, cetuximab and panitumumab. Such infusion reactions include chills, pyrexia and dizziness, which are often associated with hypersensitivity and allergic symptoms such as urticaria. Severe infusion reactions may be life-threatening and include anaphylactoid symptoms such as dyspnea, bronchospasm, hypotension, loss of consciousness and shock, or even myocardial infarction or cardiac arrest in some patients. Infusion related reactions are assigned grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.0) as follows. Grade 1 includes a mild transient reaction, wherein interruption of infusion and/or interventions is not indicated. Grade 2 includes reactions that indicate the therapy or infusion should be interrupted, but the reaction responds promptly to symptomatic treatment (e.g., NSAIDS, narcotics, or intravenous (i.v.) fluids). In such cases, prophylactic medications are indicated for up to 24 hours at the discretion of the physician or staff. Grade 3 reactions include prolonged infusion related reactions (e.g., reactions not rapidly responsive to symptomatic medication and/or a brief interruption of infusion), a recurrence of symptoms following initial improvement, and hospitalization indicated for clinical sequelae. Grade 4 includes infusion related reactions with life-threatening consequences, and urgent intervention indicated as well as cessation of infusion. Grade 5 includes infusion related reactions causing the death of the patient.
Anti-EGFR antibodies provide beneficial therapy for various cancers, but may be ineffective or lose effectiveness over time. Newer EGFR inhibitory antibody preparations are in development, including oligoclonal mixtures of anti-EGFR monoclonal antibodies. Oligoclonal anti-EGFR antibody mixtures represent a recent advance in anti-EGFR cancer therapy and have been shown preclinically to provide superior anti-cancer therapeutic effects. MM-151 and Sym004 are oligoclonal mixtures of antibodies that bind to the extracellular domain of EGFR and inhibit EGFR activity. MM-151 comprises a formulation in a pharmaceutically acceptable carrier of a triple combination of monoclonal antibody P1X, monoclonal antibody P2X, and monoclonal antibody P3X at a P1X:P2X:P3X molar ratio of 2:2:1. These experimental therapies are designed to be more potent than first generation anti-EGFR monoclonal antibodies, and thus require specially adapted dosing and administration schedules and procedures.
Thus, there is an unmet need to develop and implement methods of safely and effectively administering novel antibody-comprising therapeutics, including methods for preventing and ameliorating infusion reactions in patients, e.g., cancer patients receiving such therapeutics. The following disclosure provides such methods and confers additional advantages.